(2R,2'S)-2-(1'-Boc-2'-pyrrolidinyl)-7-hydroxy-1,4-benzodioxane | 1338384-90-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (2R,2'S)-2-(1'-Boc-2'-pyrrolidinyl)-7-hydroxy-1,4-benzodioxane
• 英文别名: tert-butyl (2S)-2-[(3R)-6-hydroxy-2,3-dihydro-1,4-benzodioxin-3-yl]pyrrolidine-1-carboxylate
• CAS: 1338384-90-9
• 化学式: C₁₇H₂₃NO₅
• 分子量: 321.373
• InChiKey: QACCTGYEWUDIOL-WFASDCNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,2'S)-2-(1'-Boc-2'-pyrrolidinyl)-7-hydroxy-1,4-benzodioxane 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以30%的产率得到(2R,2'S)-2-(2'-pyrrolidinyl)-7-hydroxy-1,4-benzodioxane
  参考文献：
  名称：

  Unichiral 2-(2′-Pyrrolidinyl)-1,4-benzodioxanes: the 2R,2′S Diastereomer of the N-Methyl-7-hydroxy Analogue Is a Potent α4β2- and α6β2-Nicotinic Acetylcholine Receptor Partial Agonist

  摘要：

  A series of unichiral 7-substituted 2-(1'-methyl-2'pyrrolidinyl)-1,4-benzodioxanes were synthesized and tested for the affinity for the alpha 4 beta 2 and alpha 7 central nicotinic receptors; the 2R,2'S diastereomer of the 7-OH analogue [(R,S)-7], unique in the series, has a high alpha 4 beta 2 affinity (12nM K-i). N-Demethylation and configuration inversion of the stereocenters greatly weaken its alpha 4 beta 2 affinity, confirming that such a rigid molecule can be considered a new template for alpha 4 beta 2 ligands. Docking analysis showed how (R,S)-7 is capable of strongly and specifically interacting with the amino acidic counterpart of the alpha 4 beta 2 receptor binding site. Further pharmacological characterization demonstrated that (R,S)-7 also has a high affinity for the alpha 6 beta 2 receptor, and in vitro functional tests indicated that it is a potent alpha 4 beta 2 and alpha 6 beta 2 partial agonist, with modest affinity and potency for the alpha 3 beta 4 receptor. Comparison with varenicline, a well-known nicotinic partial agonist used as a smoking cessation aid, interestingly reveals similar nicotinoid profiles.

  DOI：

  10.1021/jm200937t
• 作为产物：
  描述：

  (1S,2'S)-1-(1'-Boc-2'-pyrrolidinyl)-2-(o,p-dihydroxyphenoxy)ethyl mesylate 在 potassium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 反应 6.0h， 以79%的产率得到(2R,2'S)-2-(1'-Boc-2'-pyrrolidinyl)-7-hydroxy-1,4-benzodioxane
  参考文献：
  名称：

  Unichiral 2-(2′-Pyrrolidinyl)-1,4-benzodioxanes: the 2R,2′S Diastereomer of the N-Methyl-7-hydroxy Analogue Is a Potent α4β2- and α6β2-Nicotinic Acetylcholine Receptor Partial Agonist

  摘要：

  A series of unichiral 7-substituted 2-(1'-methyl-2'pyrrolidinyl)-1,4-benzodioxanes were synthesized and tested for the affinity for the alpha 4 beta 2 and alpha 7 central nicotinic receptors; the 2R,2'S diastereomer of the 7-OH analogue [(R,S)-7], unique in the series, has a high alpha 4 beta 2 affinity (12nM K-i). N-Demethylation and configuration inversion of the stereocenters greatly weaken its alpha 4 beta 2 affinity, confirming that such a rigid molecule can be considered a new template for alpha 4 beta 2 ligands. Docking analysis showed how (R,S)-7 is capable of strongly and specifically interacting with the amino acidic counterpart of the alpha 4 beta 2 receptor binding site. Further pharmacological characterization demonstrated that (R,S)-7 also has a high affinity for the alpha 6 beta 2 receptor, and in vitro functional tests indicated that it is a potent alpha 4 beta 2 and alpha 6 beta 2 partial agonist, with modest affinity and potency for the alpha 3 beta 4 receptor. Comparison with varenicline, a well-known nicotinic partial agonist used as a smoking cessation aid, interestingly reveals similar nicotinoid profiles.

  DOI：

  10.1021/jm200937t

文献信息

• Unichiral 2-(2′-Pyrrolidinyl)-1,4-benzodioxanes: the 2<i>R</i>,2′<i>S</i> Diastereomer of the <i>N</i>-Methyl-7-hydroxy Analogue Is a Potent α4β2- and α6β2-Nicotinic Acetylcholine Receptor Partial Agonist
  作者：Cristiano Bolchi、Cecilia Gotti、Matteo Binda、Laura Fumagalli、Luca Pucci、Francesco Pistillo、Giulio Vistoli、Ermanno Valoti、Marco Pallavicini

  DOI：10.1021/jm200937t

  日期：2011.11.10

  A series of unichiral 7-substituted 2-(1'-methyl-2'pyrrolidinyl)-1,4-benzodioxanes were synthesized and tested for the affinity for the alpha 4 beta 2 and alpha 7 central nicotinic receptors; the 2R,2'S diastereomer of the 7-OH analogue [(R,S)-7], unique in the series, has a high alpha 4 beta 2 affinity (12nM K-i). N-Demethylation and configuration inversion of the stereocenters greatly weaken its alpha 4 beta 2 affinity, confirming that such a rigid molecule can be considered a new template for alpha 4 beta 2 ligands. Docking analysis showed how (R,S)-7 is capable of strongly and specifically interacting with the amino acidic counterpart of the alpha 4 beta 2 receptor binding site. Further pharmacological characterization demonstrated that (R,S)-7 also has a high affinity for the alpha 6 beta 2 receptor, and in vitro functional tests indicated that it is a potent alpha 4 beta 2 and alpha 6 beta 2 partial agonist, with modest affinity and potency for the alpha 3 beta 4 receptor. Comparison with varenicline, a well-known nicotinic partial agonist used as a smoking cessation aid, interestingly reveals similar nicotinoid profiles.